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ALS-02-v1
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1 RECOVER 2.0 Worksheet
2 QUESTION ID: ALS-02
3
PICO Question:
In cats and dogs with a shockable rhythm that are being defibrillated (P), does the use of amiodarone (I) compared to not using amiodarone (C) improve outcome?
4
Outcomes:
Favorable neurologic outcome, Surrogate marker(s) of perfusion, Survival to Discharge,ROSC
5 Prioritized Outcomes (1= most critical; final number = least important):
6 1. Favorable neurologic outcome
7 2. Survival to discharge
8 3. ROSC
9 4. Surrogate markers of perfusion
10
Domain chairs: Gareth Buckley, Elizabeth Rozanski (Fletcher), Jake Wolf
11 Evidence evaluators: Alexander Thomson, Joseph DeFulio
12 Conflicts of interest: None
13 Search strategy: See attached document
14 Evidence Review:
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15 Study Design |
16 Reduced Quality Factors
17 0 = no serious, - = serious,
18 - - = very serious |
19 Positive Quality Factors
20 0 = none, + = one, ++ = multiple |
21 Dichotomous Outcome Summary |
22 Non-Dichotomous Outcome Summary
23 Brief description |
24 Overall Quality
25
High, moderate, low, |
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26 No of studies |
27 Study Type |
28 RoB |
29 Indirectness |
30 Imprecision |
31 Inconsistency |
32 Large Effect |
33 Dose-Response |
34 Confounder |
35 # Intervention with Outcome |
36 # Control with Outcome |
37 RR (95% CI) |
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38 Outcome: Favorable neurologic outcome |
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39 3 |
40 CT |
41 0 |
42 - |
43 0 |
44 0 |
45 0 |
46 0 |
47 0 |
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48 Moderate |
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49 2 |
50 OS |
51 0 |
52 - |
53 - |
54 0 |
55 0 |
56 0 |
57 0 |
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58 Very low |
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59 0 |
60 ES |
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61 Outcome: Survival to discharge |
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62 3 |
63 CT |
64 0 |
65 - |
66 0 |
67 0 |
68 0 |
69 0 |
70 0 |
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71 Moderate |
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72 8 |
73 OS |
74 0 |
75 - |
76 - |
77 - |
78 0 |
79 0 |
80 0 |
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81 Low |
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82 4 |
83 ES |
84 0 |
85 - |
86 - |
87 - |
88 0 |
89 0 |
90 0 |
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91 Low |
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92 Outcome: ROSC |
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93 1 |
94 CT |
95 0 |
96 - |
97 0 |
98 0 |
99 0 |
100 0 |
101 0 |
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102 Moderate |
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103 2 |
104 OS |
105 0 |
106 - |
107 0 |
108 0 |
109 0 |
110 0 |
111 0 |
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112 Very low |
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113 7 |
114 ES |
115 0 |
116 - |
117 - |
118 - |
119 0 |
120 0 |
121 0 |
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122 Very low |
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123 Outcome: Surrogate markers of perfusion |
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124 0 |
125 CT |
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126 0 |
127 OS |
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128 11 |
129 ES |
130 0 |
131 - |
132 - |
133 - |
134 0 |
135 0 |
136 0 |
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137 Very low |
138 PICO Question Summary
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139 Introduction |
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140 The gold-standard for treatment of PVT and VF is basic life support and defibrillation. However, the role of adjunctive therapies for shock-resistant PVT or VF is unclear. Current veterinary guidelines state that in dogs with shock-resistant PVT or VF, amiodarone may be considered.1 In human medicine, the role of antiarrhythmics (amiodarone, lidocaine, bretylium, nifekalant, etc.) during CPR remains unclear. This PICO question investigated whether amiodarone is efficacious as adjunctive therapy in dogs and cats with shockable arrest rhythms.
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141 Consensus on science |
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142 Outcome 1: Favorable neurologic outcome
143 For the most critical outcome of favorable neurologic outcome, 3 clinical trials in adult humans (moderate quality of evidence downgraded for serious indirectness) and 2 observational studies, one in children and one in adult humans, were identified (very low quality of evidence downgraded for serious indirectness and imprecision).2–6 The clinical trials were double-blinded and evaluated adults with non-traumatic out-of-hospital cardiac arrest and shock-refractory VF or PVT (defined as persistent or recurrent shockable rhythms after one or more shocks anytime during resuscitation). Patients were randomized to receive amiodarone, lidocaine, or placebo following vasopressor administration. Neither amiodarone nor lidocaine resulted in a more favorable neurologic outcome compared to placebo.2–4 The observational studies found no difference between lidocaine and amiodarone for favorable neurologic outcome with refractory PVT or VF; however, no control group was used in these studies.5,6 One study showed increased defibrillation success after 3 shocks in patients receiving amiodarone compared to patients receiving lidocaine.6
144 Outcome 2: Survival to discharge
145 For the second most critical outcome of survival to discharge, the same 3 clinical trials in adults were identified. In addition, 8 observational studies in humans (very low quality of evidence downgraded for serious indirectness) and four experimental studies in pigs (low quality of evidence downgraded for serious indirectness and imprecision) were identified.5–16 One of the clinical trials showed that for witnessed arrests, patients administered lidocaine or amiodarone had significantly higher survival to discharge when compared to placebo.3 Additionally, lidocaine and amiodarone recipients required fewer shocks, but there was no difference in survival to discharge.2 Furthermore, one study showed that amiodarone or lidocaine administered intravenously, but not intraosseously, was associated with significantly improved survival to discharge compared to placebo.4 Many of the observational studies lacked a control population, complicating their interpretation. Many of these studies compared antiarrhythmics to one another (lidocaine versus amiodarone, nifekalant versus amiodarone); the majority found no difference in survival to discharge between different antiarrhythmics. Interestingly, in a study of adults with non-traumatic cardiac arrest, Huang et al. found that survival to ICU admission, survival to discharge, and 1-year survival were highest when patients with refractory shockable rhythms were given both lidocaine and amiodarone.12 Survival to discharge was less likely in those only administered amiodarone, lower still in those only administered lidocaine, and lowest in those receiving neither. Ji et al. demonstrated higher ROSC and 24 hour survival, decreased number of shocks, lower defibrillation energy, epinephrine dose, and duration of CPR in pigs with refractory shockable rhythms administered amiodarone or nifekalant when compared to saline.13 Similarly, Zoerner et al. found greater 3-hour survival in pigs administered amiodarone in a hemorrhagic shock VF model.16 However, Karlis et al. found higher survival with nifekalant compared to amiodarone and saline and no difference in 48 hour survival between the control and amiodarone groups.15 Similarly, Glover et al. found no difference in survival between amiodarone and placebo. 14
146 Outcome 3: ROSC
147 For the next most important outcome of ROSC, we evaluated 1 clinical trial (low quality of evidence, downgraded for serious indirectness), 2 observational studies (very low quality of evidence, downgraded for serious indirectness) and 7 experimental studies (very low quality of evidence, downgraded for serious indirectness, serious imprecision, and serious inconsistency), 3 in dogs and 4 in swine. The clinical trial and 2 observational studies showed no difference in frequency of ROSC with the use of amiodarone in patients with refractory shockable rhythms.2,7,8 The experimental studies had heterogenous study designs, but overall 1 of 4 swine studies and 2 of 3 canine studies showed improvement in the frequency of ROSC in animals receiving amiodarone.13,17,18 The remainder of the studies showed no difference in ROSC between the amiodarone and control groups.15,16,19,20
148 Outcome 4: Surrogate markers of perfusion
149 For the outcome of surrogate markers of perfusion, 9 experimental studies were identified (very low quality of evidence, downgraded for serious indirectness, imprecision, and inconsistency). It is important to note that multiple experimental studies demonstrated lower coronary perfusion pressure in dogs and pigs administered amiodarone in the absence of concurrent vasopressor therapy13,18,19 The vasodilatory effects of amiodarone may be reduced when epinephrine is administered concurrently with amiodarone.17 It should also be noted that IV amiodarone does not appear to increase the defibrillation threshold, unlike oral amiodarone.21,22 Of the 9 studies, 4 were in dogs. Two showed improvement in surrogate markers of perfusion in dogs with refractory shockable rhythms with the addition of amiodarone, 1 showed no difference, and 1 showed worsened surrogate markers of perfusion.17–19,23 |
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150 Treatment recommendation |
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151 If lidocaine is unavailable, we suggest that amiodarone may be administered intravenously (5 mg/kg) during CPR for PVT or VF refractory to the first shock in dogs (weak recommendation, very low quality of evidence).
152 We suggest that amiodarone may be administered intravenously (5 mg/kg) during CPR for PVT or VF refractory to the first shock in cats (weak recommendation, very low quality of evidence).
153 We recommend against the use of amiodarone formulations containing polysorbate-80 in dogs due to the adverse hemodynamic side effects of these formulations that have been documented (strong recommendation, moderate quality of evidence). |
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154 Justification of treatment recommendation |
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155 Clinical trials and observational studies in people and experimental studies in pigs and dogs found conflicting results for the efficacy of amiodarone for the treatment of refractory PVT and VF. Many of the observational studies lacked a placebo group (instead comparing lidocaine to amiodarone therapy), complicating their interpretation. There is very little evidence suggesting that amiodarone is superior to lidocaine in these studies. The evidence of profound adverse hemodynamic effects in dogs of amiodarone formulations containing polysorbate-80 indicates that these formulations should not be used during CPR in dogs.24 The alternative aqueous formulations of amiodarone are reportedly safer25, but they are pre-diluted to a low concentration, requiring infusion of large volumes (approximately 3.3 ml/kg) to achieve the recommended dose, which may be impractical during CPR. There is one case report of successful treatment of VT in a cat using the aqueous formulation of amiodarone.26 For these reasons, the committee suggests that amiodarone can be used for dogs and cats with PVT or VF refractory to an initial attempt at defibrillation, but if lidocaine is available, it is the more practical and safer drug in dogs.
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156 Knowledge gaps |
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157 There are no controlled studies evaluating amiodarone administration in dogs and cats with spontaneous CPA and amiodarone has not been evaluated in cats. The optimal timing and dosage for amiodarone administration during CPR is unknown. Additionally, whether amiodarone should be administered concurrently with lidocaine to improve outcomes is unknown. Compared to human medicine, shockable rhythms in veterinary medicine appear less common.[ Hohene, in press] Therefore, the role of amiodarone for management of refractory pVT or VF is considered a low-priority knowledge gap in the veterinary literature.
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158 References:
159 1. Fletcher DJ, Boller M, Brainard BM, et al. RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 7: Clinical guidelines: RECOVER clinical guidelines. J Vet Emerg Crit Care. 2012;22(s1):S102-S131.
160 2. Kudenchuk PJ, Leroux BG, Daya M, et al. Antiarrhythmic Drugs for Nonshockable-Turned-Shockable Out-of-Hospital Cardiac Arrest: The ALPS Study (Amiodarone, Lidocaine, or Placebo). Circulation. 2017;136(22):2119-2131.
161 3. Kudenchuk PJ, Brown SP, Daya M, et al. Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. N Engl J Med. 2016;374(18):1711-1722.
162 4. Daya MR, Leroux BG, Dorian P, et al. Survival After Intravenous Versus Intraosseous Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Shock-Refractory Cardiac Arrest. Circulation. 2020;141(3):188-198.
163 5. Holmberg MJ, Ross CE, Atkins DL, et al. Lidocaine versus amiodarone for pediatric in-hospital cardiac arrest: An observational study. Resuscitation. 2020;149:191-201.
164 6. Wang CH, Chang WT, Huang CH, et al. Outcomes associated with amiodarone and lidocaine for the treatment of adult in-hospital cardiac arrest with shock-refractory pulseless ventricular tachyarrhythmia. J Formos Med Assoc. 2020;119(1 Pt 2):327-334.
165 7. Valdes SO, Donoghue AJ, Hoyme DB, et al. Outcomes associated with amiodarone and lidocaine in the treatment of in-hospital pediatric cardiac arrest with pulseless ventricular tachycardia or ventricular fibrillation. Resuscitation. 2014;85(3):381-386.
166 8. Pollak PT, Wee V, Al-Hazmi A, Martin J, Zarnke KB. The use of amiodarone for in-hospital cardiac arrest at two tertiary care centres. Can J Cardiol. 2006;22(3):199-202.
167 9. Amino M, Inokuchi S, Nagao K, et al. Nifekalant Hydrochloride and Amiodarone Hydrochloride Result in Similar Improvements for 24-Hour Survival in Cardiopulmonary Arrest Patients: The SOS-KANTO 2012 Study. J Cardiovasc Pharmacol. 2015;66(6):600-609.
168 10. Tagami T, Matsui H, Tanaka C, et al. Amiodarone Compared with Lidocaine for Out-Of-Hospital Cardiac Arrest with Refractory Ventricular Fibrillation on Hospital Arrival: a Nationwide Database Study. Cardiovasc Drugs Ther. 2016;30(5):485-491.
169 11. Tagami T, Matsui H, Ishinokami S, et al. Amiodarone or nifekalant upon hospital arrival for refractory ventricular fibrillation after out-of-hospital cardiac arrest. Resuscitation. 2016;109:127-132.
170 12. Huang CH, Yu PH, Tsai MS, et al. Acute hospital administration of amiodarone and/or lidocaine in shockable patients presenting with out-of-hospital cardiac arrest: A nationwide cohort study. Int J Cardiol. 2017;227:292-298.
171 13. Ji XF, Li CS, Wang S, Yang L, Cong LH. Comparison of the efficacy of nifekalant and amiodarone in a porcine model of cardiac arrest. Resuscitation. 2010;81(8):1031-1036.
172 14. Glover BM, Hu X, Aves T, et al. Dronedarone and captisol-enabled amiodarone in an experimental cardiac arrest. J Cardiovasc Pharmacol. 2013;61(5):385-390.
173 15. Karlis G, Iacovidou N, Lelovas P, et al. Nifekalant Versus Amiodarone in the Treatment of Cardiac Arrest: an Experimental Study in a Swine Model of Prolonged Ventricular Fibrillation. Cardiovasc Drugs Ther. 2015;29(5):425-431.
174 16. Zoerner F, Semenas E. Resuscitation with amiodarone increases survival after hemorrhage and ventricular fibrillation in pigs. J Trauma Acute Care Surg. 2014;76(6):1402-1408.
175 17. Wira C, Martin G, Stoner J, Margolis K, Donnino M. Application of normothermic cardiac arrest algorithms to hypothermic cardiac arrest in a canine model. Resuscitation. 2006;69(3):509-516.
176 18. Anastasiou-Nana MI, Nanas JN, Nanas SN, et al. Effects of amiodarone on refractory ventricular fibrillation in acute myocardial infarction: experimental study. J Am Coll Cardiol. 1994;23(1):253-258.
177 19. Stoner J, Martin G, O’Mara K, Ehlers J, Tomlanovich M. Amiodarone and bretylium in the treatment of hypothermic ventricular fibrillation in a canine model. Acad Emerg Med. 2003;10(3):187-191.
178 20. Wiesmann T, Freitag D, Dersch W, et al. Dantrolene versus amiodarone for cardiopulmonary resuscitation: A randomized, double-blinded experimental study. Sci Rep. 2017;7.
179 21. FRAME LH. The Effect of Chronic Oral and Acute Intravenous Amiodarone Administration on Ventricular Defibrillation Threshold Using Implanted Electrodes in Dogs. Pacing Clin Electrophysiol. 1989;12(2):339-346.
180 22. Fain ES, Lee JT, Winkle RA. Effects of acute intravenous and chronic oral amiodarone on defibrillation energy requirements. Am Heart J. 1987;114(1 PART 1):8-17.
181 23. Arredondo MT, Guillen SG, Quinteiro RA. Effect of amiodarone on ventricular fibrillation and defibrillation thresholds in the canine heart under normal and ischemic conditions. Eur J Pharmacol. 1986;125(1):23-28.
182 24. Masini E, Planchenault J, Pezziardi F, Gautier P, Gagnol JP. Histamine-releasing properties of Polysorbate 80 in vitro and in vivo: correlation with its hypotensive action in the dog. Agents Actions. 1985;16(6):470-477.
183 25. Levy NA, Koenigshof AM, Sanders RA. Retrospective evaluation of intravenous premixed amiodarone use and adverse effects in dogs (17 cases: 2011-2014). J Vet Cardiol Off J Eur Soc Vet Cardiol. 2016;18(1):10-14.
184 26. Berlin N, Ohad DG, Maiorkis I, Kelmer E. Successful management of ventricular fibrillation and ventricular tachycardia using defibrillation and intravenous amiodarone therapy in a cat. J Vet Emerg Crit Care San Antonio. Published online 2020.
185 Additional References:
186 Masini E, Planchenault J, Pezziardi F, Gautier P, Gagnol JP. Histamine-releasing properties of Polysorbate 80 in vitro and in vivo: correlation with its hypotensive action in the dog. Agents Actions. 1985; 16: 470–477.
187 Levy NA, Koenigshof AM, Sanders RA. Retrospective evaluation of intravenous premixed amiodarone use and adverse effects in dogs (17 cases: 2011-2014). J Vet Cardiol. 2016 Mar;18(1):10-4. doi: 10.1016/j.jvc.2015.10.009. Epub 2016 Jan 21. PMID: 26803199.
188 Berlin N, Ohad DG, Maiorkis I, Kelmer E. Successful management of ventricular fibrillation and ventricular tachycardia using defibrillation and intravenous amiodarone therapy in a cat. J Vet Emerg Crit Care (San Antonio). 2020 Jul;30(4):474-480. doi: 10.1111/vec.12960. Epub 2020 May 13. PMID: 32400960
189 Supplemental Information:
190 Outcome: Favorable neurologic outcome
191 3 Clinical Trials
192 Kudenchuk et al., 2016: Amiodarone, lidocaine, or placebo in OOHCA
193 ● Randomized, double blind trial of adults with non-traumatic OOHCA and shock refractory VF or PVT (shock refractory: persistent or recurrent shockable rhythm after one or more shocks anytime during resuscitation)
194 ● Patients then randomized to receive amiodarone, lidocaine, or placebo after a vasopressor
195 ● Neither amiodarone nor lidocaine resulted in a higher survivor or favorable neuro outcome than placebo
196 ● With witnessed arrest, lidocaine and amiodarone had significantly higher survival than placebo
197 Kudenchuk et al., 2017: Antiarrhythmic drugs for nonshockable turned shockable OOHCA
198 ● Adults with nontraumatic OOHCA and VF/PVT anytime after one or more shocks randomized to placebo, lidocaine, or amiodarone
199 ● 3026 with VF/PVT and 1063 with nonshockable turned shockable
200 ● Non-statistically significant increase in survival (and improved neuro outcome) with amiodarone or lidocaine compared to placebo
201 ● Active-drug recipients in this cohort required fewer shocks, supplemental doses of their assigned drug, and ancillary antiarrhythmic drugs than recipients of a placebo
202 ● Survival approached significance (p 0.08) for nonshockable turned shockable rhythms with amiodarone compared to placebo
203 Daye et al., 2020: Survival after IV versus IO amiodarone, lidocaine, or placebo in OOH shock-refractory cardiac arrest
204 ● Same study population as previous study
205 ● Amiodarone and lidocaine associated with more favorable neuro outcome when administered IV, but not IO when compared to placebo (as was survival to discharge and survival to hospital admission)
206 2 Observational Studies
207 Holmberg et al., 2020: Lidocaine versus amiodarone for pediatric in hospital cardiac arrest: an observational study
208 ● From registry, included children with IHCA with an initial or subsequent shockable rhythm and then matched based on a propensity score
209 ● No difference between lidocaine and amiodarone for survival, ROSC, or favorable neuro outcome
210 Wang et al., 2020: Outcomes associated with amiodarone and lidocaine for the treatment for adult IHCA with shock refractory pulseless ventricular tachyarrhythmia
211 ● Included 130 patients with IHCA and VF/pVT requiring more than one defibrillation attempt
212 ● No control group. No difference in ROSC, survival or favorable neuro outcome for lidocaine v amiodarone. Amiodarone group experienced a higher likelihood of terminating VF/pVT within three shocks
213 0 Experimental Studies
214 Outcome: Survival to discharge
215 3 Clinical Trials
216 Kudenchuk et al., 2016: Amiodarone, lidocaine, or placebo in OOHCA
217 ● Randomized, double blind trial of adults with non-traumatic OOHCA and shock refractory VF or PVT (shock refractory: persistent or recurrent shockable rhythm after one or more shocks anytime during resuscitation). Patients then randomized to receive amiodarone, lidocaine, or placebo after a vasopressor
218 ● Neither amiodarone nor lidocaine resulted in a higher survivor or favorable neuro outcome than placebo
219 ● With witnessed arrest, lidocaine and amiodarone had significantly higher survival than placebo
220 Kudenchuk et al., 2017: Antiarrhythmic drugs for nonshockable turned shockable OOHCA
221 ● Adults with nontraumatic OOHCA and VF/PVT anytime after one or more shocks randomized to placebo, lidocaine, or amiodarone
222 ● 3026 with VF/PVT and 1063 with nonshockable turned shockable
223 ● Non-statistically significant increase in survival (and improved neuro outcome) with amiodarone or lidocaine compared to placebo
224 ● Survival approached significance (p 0.08) for nonshockable turned shockable rhythms with amiodarone compared to placebo
225 Daye et al., 2020: Survival after IV versus IO amiodarone, lidocaine, or placebo in OOH shock-refractory cardiac arrest
226 ● Same study population as previous study
227 ● Amiodarone and lidocaine associated with more survival to discharge and survival to hospital admission when administered IV, but not IO when compared to placebo
228 8 Observational Studies
229 Valdes et al., 2014: Outcomes associated with amiodarone and lidocaine in the treatment of in hospital pediatric cardiac arrest with pVT or VF
230 ● Retrospective cohort study for inpatient cardiac arrest in 889 patients
231 ● Lidocaine associated with improved ROSC and 24 hour survival but not hospital discharge. Amiodarone not associated with ROSC or survival
232 Pollak et al., 2006: The use of amiodarone for in hospital cardiac arrest at two tertiary care centres
233 ● 374 charts retrospectively examined; shockable rhythms present in 95 patients
234 ● No difference in ROSC or survival between amiodarone and patients receiving only other antiarrhythmics (though amiodarone trended towards lower ROSC and survival)
235 Holmberg et al., 2020: Lidocaine versus amiodarone for pediatric in hospital cardiac arrest: an observational study
236 ● From registry, included children with IHCA with an initial or subsequent shockable rhythm and then matched based on a propensity score
237 ● No difference between lidocaine and amiodarone for survival, ROSC, or favorable neuro outcome
238 Wang et al., 2020: Outcomes associated with amiodarone and lidocaine for the treatment for adult IHCA with shock refractory pulseless ventricular tachyarrhythmia
239 ● Included 130 patients with IHCA and VF/pVT requiring more than one defibrillation attempt
240 ● No control group. No difference in ROSC, survival or favorable neuro outcome for lidocaine v amiodarone.
241 Amino et al., 2015: Nifekalant hydrochloride and amiodarone hydrochloride result in similar improvements for 24 hours survival in CPA patients: the SOS-KANTO 2012 study
242 ● Enrolled 500 adults with OOHCA who used a single antiarrhythmic for shock resistant VF/VT. Survival to admission significantly higher with amiodarone and nifekalant compared to lidocaine and 24 hour survival. ROSC not different between groups
243 Tagami et al., 2016: Amiodarone or nifekalant upon hospital arrival for refractory VF after OOHCA
244 ● Retrospective cohort study of adults with cardiogenic OOHCA and with VF on hospital arrival classified into amiodarone or nifekalant groups. From there, propensity matching occurred
245 ● Amiodarone significantly less likely to be admitted to hospital but no difference in in hospital mortality
246 Tagami et al., 2016: Amiodarone compared with lidocaine for OOHCA with refractory VF on hospital arrival: a nationwide database study
247 ● Same procedure as above but categorized into amiodarone or lidocaine groups
248 ● No difference in survival to hospital discharge
249 Huang et al., 2017: Acute hospital administration of amiodarone and/or lidocaine in shockable patients presenting with OOHCA: a nationwide cohort study
250 ● Repository for insurance claims in Taiwan was searched. Included all non-traumatic adults receiving shock and CPR immediately or within 6 hours of ER arrival
251 ● Better survival to ICU admission, discharge, and 1 year survival when given both lidocaine and amiodarone (over amiodarone, then lidocaine, then neither). In intergroup comparisons, no difference between patients given one or both medications
252 4 Experimental Studies
253 Ji et al., 2010: Comparison of the efficacy of nifekalant and amiodarone in a porcine model of cardiac arrest
254 ● 4 minutes of untreated VF in 36 pigs randomized to amiodarone, placebo, or nifekalant. CPR initiated after drug admin and defibrillation attempted 2 minutes later
255 ● Nifekalant and amiodarone decreased number of shocks, defibrillation energy, epi dose, and duration of CPR. Higher ROSC and 24 hour survival in both groups. Improved postresuscitation myocardial dysfunction with treatment
256 Glover et al., 2013: Dronedarone and captisol enabled amiodarone in an experimental cardiac arrest
257 ● 42 pigs had induced VF, CPR for 3 minutes and then randomized to receive placebo, amiodarone, or dronedarone, followed by defibrillation and continued CPR
258 ● No difference in survival with amiodarone admin compared to control. Worse survival with dronedarone
259 Karlis et al., 2015: Nifekalant versus amiodarone in the treatment of cardiac arrest: an experimental study in a swine model of prolonged VF
260 ● 8 minutes of untreated VF followed by bolus of epi and either nifekalant, amiodarone, or saline in pigs. Then CPR and defibrillation after 2 minutes
261 ● Higher survival with nifekalant v amiodarone and saline. Higher SAP, DAP, and CPP with nifekalant. Number of shocks needed, time to ROSC, and epi dose higher with amiodarone. No difference in 48 hour survival between control and amiodarone
262 Zoerner et al., 2014: Resuscitation with amiodarone increases survival after hemorrhage and VF in pigs
263 ● 18 anesthetized piglets bled 30% blood volume to MAP of 35 mmHg followed by 4 minutes of VF and 11 minutes of open chest CPR. At 4 minutes received either amiodarone or saline. Both groups received hypertonic-hyperoncotic solution and vasopressin at this time. Defibrillation attempted from 7 min of cardiac arrest
264 ● Greater 3 hour survival in amiodarone group; also had lower HR and better SAP, DAP, and MAP. Lower troponin I and higher UOP
265 Outcome: ROSC
266 1 Clinical Trial
267 Kudenchuk et al., 2017: Antiarrhythmic drugs for nonshockable turned shockable OOHCA
268 ● Adults with nontraumatic OOHCA and VF/PVT anytime after one or more shocks randomized to placebo, lidocaine, or amiodarone
269 ● 3026 with VF/PVT and 1063 with nonshockable turned shockable
270 ● No difference in ROSC
271 2 Observational Studies
272 Valdes et al., 2014: Outcomes associated with amiodarone and lidocaine in the treatment of in hospital pediatric cardiac arrest with pVT or VF
273 ● Retrospective cohort study for inpatient cardiac arrest in 889 patients
274 ● Lidocaine associated with improved ROSC and 24 hour survival but not hospital discharge. Amiodarone not associated with ROSC or survival
275 Pollak et al., 2006: The use of amiodarone for in hospital cardiac arrest at two tertiary care centres
276 ● 374 charts retrospectively examined; shockable rhythms present in 95 patients
277 ● No difference in ROSC or survival between amiodarone and patients receiving only other antiarrhythmics (though amiodarone trended towards lower ROSC and survival)
278 Salcido et al., 2018: Effects of intra-resuscitation antiarrhythmic administration on rearrest occurrence and intra-resuscitation ECG characteristics in the ROC ALPS trial
279 ● Secondary analysis of the ALPS trial listed above
280 ● ALPS treatment group (placebo, lidocaine, or amiodarone) was not associated with rearrest
281 Holmberg et al., 2020: Lidocaine versus amiodarone for pediatric in hospital cardiac arrest: an observational study
282 ● From registry, included children with IHCA with an initial or subsequent shockable rhythm and then matched based on a propensity score
283 ● No difference between lidocaine and amiodarone for survival, ROSC, or favorable neuro outcome
284 Wang et al., 2020: Outcomes associated with amiodarone and lidocaine for the treatment for adult IHCA with shock refractory pulseless ventricular tachyarrhythmia
285 ● Included 130 patients with IHCA and VF/pVT requiring more than one defibrillation attempt
286 ● No control group. No difference in ROSC, survival or favorable neuro outcome for lidocaine v amiodarone.
287 Amino et al., 2015: Nifekalant hydrochloride and amiodarone hydrochloride result in similar improvements for 24 hours survival in CPA patients: the SOS-KANTO 2012 study
288 ● Enrolled 500 adults with OOHCA who used a single antiarrhythmic for shock resistant VF/VT. Survival to admission significantly higher with amiodarone and nifekalant compared to lidocaine and 24 hour survival. ROSC not different between groups
289 7 Experimental Studies
290 Ji et al., 2010: Comparison of the efficacy of nifekalant and amiodarone in a porcine model of cardiac arrest
291 ● 4 minutes of untreated VF in 36 pigs randomized to amiodarone, placebo, or nifekalant. CPR initiated after drug admin and defibrillation attempted 2 minutes later
292 ● Nifekalant and amiodarone decreased number of shocks, defibrillation energy, epi dose, and duration of CPR. Higher ROSC and 24 hour survival in both groups. Improved postresuscitation myocardial dysfunction with treatment
293 Zoerner et al., 2014: Resuscitation with amiodarone increases survival after hemorrhage and VF in pigs
294 ● 18 anesthetized piglets bled 30% blood volume to MAP of 35 mmHg followed by 4 minutes of VF and 11 minutes of open chest CPR. At 4 minutes received either amiodarone or saline. Both groups received hypertonic-hyperoncotic solution and vasopressin at this time. Defibrillation attempted from 7 min of cardiac arrest
295 ● ROSC effects did not achieve statistical significant difference. Pigs in control group needed more vasopressin doses to achieve ROSC
296 Karlis et al., 2015: Nifekalant versus amiodarone in the treatment of cardiac arrest: an experimental study in a swine model of prolonged VF
297 ● 8 minutes of untreated VF followed by bolus of epi and either nifekalant, amiodarone, or saline in pigs. Then CPR and defibrillation after 2 minutes
298 ● Number of shocks needed, time to ROSC, and epi dose higher with amiodarone. No difference in 48 hour survival between control and amiodarone or ROSC
299 Stoner et al., 2003: Amiodarone and bretylium in the treatment of hypothermic VF in a canine model
300 ● 30 dogs anesthetized, cooled, and VF induced. CPR initiated (no epi) and randomized to receive amiodarone, bretylium or placebo. After 10 minutes, up to three shocks administered
301 ● No difference in ROSC between groups
302 Wira et al., 2006: Application of normothermic cardiac arrest algorithms to hypothermic cardiac arrest in a canine model
303 ● 21 dogs cooled to VF or VF induced if necessary. Treatment group received epi, defibrillation, and amiodarone. Not blinded
304 ● CPP increased with amiodarone/epi administration and improved ROSC
305 Anastasiou-Nana et al., 1994: Effects of amiodarone on refractory VF in acute myocardial infarction: experimental study
306 ● AMI induced in 60 dogs via ligation. Dogs that developed VF were treated with lidocaine, epi, and 5 shocks. Refractory dogs randomized to receive epi, lidocaine, and counter shocks or amiodarone and countershocks
307 ● Defibrillation significantly higher in amiodarone group
308 Wiesmann et al., 2017: Dantrolene versus amiodarone for CPR: a randomized double blinded experimental stuy
309 ● VF induced in anesthetized pigs. After 8 min untreated, CPR started and randomized to amiodarone, dantrolene, or slaine. After 4 minutes, defibrillation attempted
310 ● No difference in ROSC, persistent ROSC, or shocks until ROSC between groups
311 Outcome: Surrogate markers of perfusion
312 0 Clinical Trials
313 1 Observational Studies
314 Wang et al., 2020: Outcomes associated with amiodarone and lidocaine for the treatment for adult IHCA with shock refractory pulseless ventricular tachyarrhythmia
315 ● Included 130 patients with IHCA and VF/pVT requiring more than one defibrillation attempt
316 ● No control group. No difference in ROSC, survival or favorable neuro outcome for lidocaine v amiodarone. Amiodarone group experienced a higher likelihood of terminating VF/pVT within three shocks
317 11 Experimental Studies
318 Stoner et al., 2003: Amiodarone and bretylium in the treatment of hypothermic VF in a canine model
319 ● 30 dogs anesthetized, cooled, and VF induced. CPR initiated (no epi) and randomized to receive amiodarone, bretylium or placebo. After 10 minutes, up to three shocks administered
320 ● Amiodarone lowered CPP but did not reach statistical significance
321 Wira et al., 2006: Application of normothermic cardiac arrest algorithms to hypothermic cardiac arrest in a canine model
322 ● 21 dogs cooled to VF or VF induced if necessary. Treatment group received epi, defibrillation, and amiodarone. Not blinded
323 ● CPP increased with amiodarone/epi administration and improved ROSC
324 Ji et al., 2010: Comparison of the efficacy of nifekalant and amiodarone in a porcine model of cardiac arrest
325 ● 4 minutes of untreated VF in 36 pigs randomized to amiodarone, placebo, or nifekalant. CPR initiated after drug admin and defibrillation attempted 2 minutes later
326 ● Nifekalant and amiodarone decreased number of shocks, defibrillation energy, epi dose, and duration of CPR. Improved postresuscitation myocardial dysfunction with treatment. Amiodarone decreased HR, arterial BP, and CPP
327 Glover et al., 2013: Dronedarone and captisol enabled amiodarone in an experimental cardiac arrest
328 ● 42 pigs had induced VF, CPR for 3 minutes and then randomized to receive placebo, amiodarone, or dronedarone, followed by defibrillation and continued CPR
329 ● No effect on surrogate markers of perfusion
330 Anastasiou-Nana et al., 1994: Effects of amiodarone on refractory VF in acute myocardial infarction: experimental study
331 ● AMI induced in 60 dogs via ligation. Dogs that developed VF were treated with lidocaine, epi, and 5 shocks. Refractory dogs randomized to receive epi, lidocaine, and counter shocks or amiodarone and countershocks
332 ● Defibrillation significantly higher in amiodarone group. Worse markers of perfusion in amiodarone group
333 Karlis et al., 2015: Nifekalant versus amiodarone in the treatment of cardiac arrest: an experimental study in a swine model of prolonged VF
334 ● 8 minutes of untreated VF followed by bolus of epi and either nifekalant, amiodarone, or saline in pigs. Then CPR and defibrillation after 2 minutes
335 ● Higher SAP, DAP, and CPP with nifekalant. Number of shocks needed, time to ROSC, and epi dose higher with amiodarone.
336 Zoerner et al., 2014: Resuscitation with amiodarone increases survival after hemorrhage and VF in pigs
337 ● 18 anesthetized piglets bled 30% blood volume to MAP of 35 mmHg followed by 4 minutes of VF and 11 minutes of open chest CPR. At 4 minutes received either amiodarone or saline. Both groups received hypertonic-hyperoncotic solution and vasopressin at this time. Defibrillation attempted from 7 min of cardiac arrest
338 ● Greater 3 hour survival in amiodarone group; also had lower HR and better SAP, DAP, and MAP. Lower troponin I and higher UOP
339 Frame, 1989: The effect of chronic oral and acute IV amiodarone administration on ventricular defibrillation threshold using implanted electrodes in dogs
340 ● VF induced and then defibrillation following oral and IV amiodarone administration
341 ● Oral amiodarone increased the fibrillation threshold. No change with IV administration. Not directly relevant to PICO, but provides important info tangential to it (amiodarone probably does not make it harder to defibrillate)
342 Fain et al., 1987: Effects of acute IV and chronic oral amiodarone on defibrillation energy requirements
343 ● VF induced and then defibrillation following oral and IV amiodarone administration
344 ● Oral amiodarone increased the fibrillation threshold. No change with IV administration. Not directly relevant to PICO, but provides important info tangential to it (amiodarone probably does not make it harder to defibrillate)
345 Paiva et al, 2003: Effect of amiodarone on haemodynamics during CPR in a canine model of resistant VF
346 ● 30 dogs with 8 minutes untreated VF, defibrillation attempted and CPR started. Resistant dogs randomized to epi, amiodarone, or both
347 ● SAP, DAP, and CPP all lower in amiodarone alone group
348 Arrendondo et al., 1986: Effect of amiodarone on ventricular fibrillation and defibrillation thresholds in the canine heart under normal and ischemic conditions
349 ● 11 dogs with VF during control, drug (amiodarone), and coronary occlusion phases
350 ● Amiodarone led to successful defibrillation in 7/8 dogs compared to 1/7 in the control group P<0.005)
General Document Comments 2
Hi Rebecca! Can you please clarify what you mean by “the previous comment?” ALS-01 suggests that lidocaine can be used in dogs but probably shouldn’t be used in cats. This PICO suggests that if lidocaine is not available, you could use amiodarone in dogs, but lidocaine is preferred. Please let us know what you mean here. Thanks!
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